Iontophoretic devices

• US 6,858,018 B1
• Filed: 09/28/1998
• Issued: 02/22/2005
• Est. Priority Date: 09/28/1998
• Status: Expired due to Fees

• Current Assignee: Vyteris, Inc.
• Original Assignee: Vyteris, Inc.
• Inventors: Green, Philip G., Brosnan-Cook, Michelle R., Pettis, Ronald J.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US09/162,301
• Time in Patent Office: 2,339 Days
• Field of Search: 424/449, 424/448, 604/19, 604/20
• US Class Current: 604/19
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Iontophoretic devices for the delivery of N-phenyl-N-(4-piperidinyl)amide esters are provided. The N-phenyl-N-(4-piperidinyl)amide esters are compounds of the 1. A reservoir comprising a matrix material and, distributed in said matrix material, a pharmaceutically acceptable amount of at least one compound selected from compounds of the formula (I)
wherein:

• • X is a member selected from the group consisting of alkoxy-carbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxy-carbonyl-lower alkyl, and (C_1-2)alkoxy-(C_1-2)alkoxy-carbonyl-lower alkyl;
  • Ar is a member selected from the group consisting of phenyl, and mono-, di- and tri-substituted phenyl, wherein each substituent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;
  • R is a member selected from the group consisting of lower alkyl, and lower alkoxy-lower alkyl,;
  • R¹ is a member selected from the group consisting of hydrogen, lower alkoxy-carbonyl; and
  • R² is a member selected from the group consisting of hydrogen and methyl; and the optically active and cis-trans isomers thereof, and the acid addition salts, of said compounds and isomers.

Claims

1. An iontophoretic device comprising:

(a) a donor reservoir comprising a matrix material and, distributed in said matrix material, a pharmaceutically acceptable amount of at least one compound selected from compounds of the formula (I)

wherein;

X is a member selected from the group consisting of;

alkoxy-carbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxy-carbonyl-lower alkyl, and (C_1-2)alkoxy-(C_1-2)alkoxy-carbonyl-lower alkyl;

Ar is a member selected from the group consisting of phenyl, and mono-, di- and tri-substituted phenyl, wherein each substituent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;

R is a member selected from the group consisting of lower alkyl, OCH₃and lower alkoxy-lower alkyl;

R¹ is a member selected from the group consisting of hydrogen, and lower alkoxy-carbonyl; and

R² is a member selected from the group consisting of hydrogen and methyl, and the optically active and cis-trans isomers thereof, and the acid addition salts of said compounds and isomers;

(b) a current distributing member in electrical communication with the donor reservoir;

(c) an indifferent electrode; and

(d) an electrical power source in electrical connection with the current distributing member and the indifferent electrode.

2. The iontophoretic device of claim 1 wherein X is alkoxy-carbonyl-lower alkyl.

3. The iontophoretic device of claim 1 wherein the at least one compound is the hydrochloride salt of the compound of formula (I) wherein X is CH₂CH₂COOCH₃, R is OCH₃, R¹ and R² are both hydrogen, and Ar is phenyl.

4. The iontophoretic device of claim 1 wherein the matrix material is a polymer gel.

5. The iontophoretic device of claim 1 wherein the matrix material is crosslinked polyvinylpyrrolidone.

6. A method for preparing an iontophoretic reservoir comprising:

distributing in a matrix material an effective amount of at least one compound of the formula (I)

wherein;

X is a member selected from the group consisting of;

alkoxy-carbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxy-carbonyl-lower alkyl, and (C_1-2)alkoxy-(C_1-2)alkoxy-carbonyl-lower alkyl;

Ar is a member selected from the group consisting of phenyl, and mono-, di- and tri-substituted phenyl, wherein each substituent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;

R is a member selected from the group consisting of lower alkyl, OCH₃ and lower alkoxy-lower alkyl;

R¹ is a member selected from the group consisting of hydrogen, and lower alkoxy-carbonyl; and

R² is a member selected from the group consisting of hydrogen and methyl, and the optically active and cis-trans isomers thereof, and the acid addition salts of said compounds and isomers.

7. The method of claim 6 wherein X is alkoxy-carbonyl-lower alkyl.

8. The method of claim 6 wherein the at least one compound is the hydrochloride salt of the compound of formula (I) wherein X is CH₂CH₂COOCH₃, R is OCH₃, R¹ and R² are both hydrogen, and Ar is phenyl.

9. The method of claim 6 wherein the matrix material is a polymer gel.

10. The method of claim 6 wherein the matrix material is crosslinked polyvinylpyrrolidone.

11. The method of claim 6, wherein the at least one compound is distributed in the matrix in an amount of from 0.01 milligrams to 1000 milligrams.